Brain natriuretic peptide (BNP) is a 32 amino acid, cardiac derived peptide hormone with potent vasodilator, natriuretic, and diuretic actions. Recent clinical studies suggest that BNP is a cardioprotective hormone secreted in response to the chronic hemodynamic and hormonal stress associated with heart disease. BNP is derived from a high molecular weight, 108 amino acid precursor protein termed proBNP. ProBNP is a significant, and in some cases, major form of BNP in the circulation. Due to the limited quantities available in the blood, nothing is known about the biological activity of proBNP compared with BNP. This grant will produce proBNP by recombinant techniques and measure its activities in vitro assays and in vivo animal models. In addition, the metabolism of proBNP in animals will be studied. These studies will assess the potential of proBNP as a therapeutic for the treatment of heart disease. As heart disease continues to be the cause of a significant percentage of total hospitalizations, morbidity, and mortality the need for new drugs for heart disease is compelling. PROPOSED COMMERCIAL APPLICATIONS Recombinant proBNP may be a useful therapeutic for the treatment of heart disease.